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Methylenetetrahydrofolate Reductase Gene Polymorphisms as Predictive and Prognostic Biomarkers in Ovarian Cancer Risk

  • Gao, Song (Department of Obstetric and Gynecology, Shengjing Hospital of China Medical University) ;
  • Liu, Ning (Department of Obstetric and Gynecology, Shengjing Hospital of China Medical University) ;
  • Ma, Yang (Department of Obstetric and Gynecology, Shengjing Hospital of China Medical University) ;
  • Ying, Liu (Department of Obstetrics and Gynecology, The Second West China Hospital, Sichuan University)
  • Published : 2012.02.29

Abstract

Early diagnosis and better prognosis of ovarian cancer is still a challenge. Besides environmental risk factors, genetic factors have established a role in pathogenesis of ovarian cancer. Methods: A case-control and a prospective study design conducted in 224 ovarian cancer patients and 432 controls in Chinese population. MTHFR C677T genotyping was done by PCR-RFLP. Results: Patients with ovarian cancer is associated with a higher less number of delivery and less frequent oral contraceptive use. When potential confounding factors adjusted logistic regression analysis between cases and controls were performed, significant association was obtained for 677T/T genotype and ovarian cancer (OR=3.13, 95% CI=1.59-5.72). Cox regression survival analysis showed individuals carrying T/T genotype had significantly increased HR for death in ovarian cancer patients (HR=2.86, 95% CI=1.27-7.93). In conclusion, we observed that the MTHFR C677T polymorphism is associated with the susceptibility and survival of ovarian cancer in Chinese population.

Keywords

Methylenetetrahydrofolate reductase gene;polymorphism;ovarian cancer risk

References

  1. Bailey LB, Gregory JF (1999). 3rd Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirement. J Nutr, 129, 919-22. https://doi.org/10.1093/jn/129.5.919
  2. Blount BC, Mack MM, Wehr CM, et al (2007). Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Proc Natl Acad Sci U S A, 94, 3290-5.
  3. Carlsson G, Hafstrom LO, Spears CP, et al (1997). 5-fluorouracil (5-FU) and 5, 10-methylene tetrahydrofolate (5, 10-CH2FH4) as adjuvant therapy in an experimental rodent colon carcinoma model. Anticancer Res, 17, 3671-4.
  4. Choi SW, Mason JB (2000). Folate and carcinogenesis: an integrated scheme. J Nutr, 13, 129-32.
  5. Cohen V, Panet-Raymond V, Sabbaghian N, et al (2003). Methylenetetrahydrofolate reductase polymorphism in advanced colorectal cancer: a novel genomic predictor of clinical response to fluoropyrimidinebased chemotherapy. Clin Cancer Res, 9, 1611-5.
  6. Frosst P, Blom HJ, Milos R, et al (1995). A candidate genetic risk factor for vascular disease: a commonmutation inmethylenetetrahydrofolate reductase. Nat Genet, 10, 111-3. https://doi.org/10.1038/ng0595-111
  7. Gallus S, La Vecchia C (2007). Is there a link between diet and esophageal cancer? Nat Clin Pract Gastroenterol Hepatol, 4, 2-3.
  8. Gershoni-Baruch R, Dagan E, Israeli D, et al (2000). Association of the C677T polymorphism in the MTHFR gene with breast and/or ovarian cancer risk in Jewish women. Eur J Cancer, 36, 2313-6. https://doi.org/10.1016/S0959-8049(00)00306-3
  9. Goode EL, Maurer MJ, Sellers TA, et al (2010). Inherited determinants of ovarian cancer survival. Clin Cancer Res, 16, 995-1007. https://doi.org/10.1158/1078-0432.CCR-09-2553
  10. Jain M, Tilak AR, Upadhyay R, et al (2008). Microsomal epoxide hydrolase (EPHX1), slow (exon 3, 113His) and fast (exon 4, 139Arg) alleles confer susceptibility to squamous cell esophageal cancer. Toxicol Appl Pharmacol, 230, 247-51. https://doi.org/10.1016/j.taap.2008.02.023
  11. Jin F, Shu XO, Devesa SS, et al (1993). Incidence trends for cancers of the breast, ovary, and corpus uteri in urban Shanghai, 1972-89. Cancer Causes Control, 4, 355-60. https://doi.org/10.1007/BF00051338
  12. Joshi G, Pradhan S, Mittal B (2009). Role of the ACE ID and MTHFR C677T polymorphisms in genetic susceptibility of migraine in a north Indian population. J Neurol Sci, 277, 133-7. https://doi.org/10.1016/j.jns.2008.11.002
  13. Kristensen, GB, Trope C (1997). Epithelial ovarian carcinoma. Lancet, 349, 113-7. https://doi.org/10.1016/S0140-6736(96)06071-0
  14. La Vecchia C (2001). Epidemiology of ovarian cancer: a summary review. Eur J Cancer Prev, 10, 125-9. https://doi.org/10.1097/00008469-200104000-00002
  15. Miller SA, Dykes DD, Polesky HF (1988). A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res, 16, 1215. https://doi.org/10.1093/nar/16.3.1215
  16. Reddy H, Jamil K (2006). Polymorphisms in the MTHFR gene and their possible association with susceptibility to childhood acute lymphocytic leukemia in an Indian population. Leuk Lymphoma, 47, 1333-9. https://doi.org/10.1080/10428190600562773
  17. Sarbia M, Stahl M, vonWeyhern C, et al (2006). The prognostic significance of genetic polymorphisms (methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, thymidilate synthase tandem repeat polymorphism) in multimodally treated oesophageal squamous cell carcinoma. Br J Cancer, 94, 203-7. https://doi.org/10.1038/sj.bjc.6602900
  18. Shen H, Spitz MR, Wang LE, et al (2001). Polymorphisms of methylene-tetrahydrofolate reductase and risk of lung cancer: a case-control study. Cancer Epidemiol Biomarkers Prev, 10, 397-401.
  19. Skibola CF, Smith MT, Kane E, et al (1999). Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults. Proc Natl Acad Sci U S A, 96, 12810-5. https://doi.org/10.1073/pnas.96.22.12810
  20. Terry KL, Tworoger SS, Goode EL, et al (2010). MTHFR polymorphisms in relation to ovarian cancer risk. Gynecol Oncol, 119, 319-24. https://doi.org/10.1016/j.ygyno.2010.08.007
  21. Upadhyay R, Jain M, Kumar S, et al (2009). Functional polymorphisms of cyclooxygenase-2 (COX-2) gene and risk for esophageal squamous cell carcinoma. Mutat Res, 663, 52-9. https://doi.org/10.1016/j.mrfmmm.2009.01.007
  22. Upadhyay R, Jain M, Kumar S, et al (2008). Association of interleukin-6 (-174G>C) promoter polymorphism with risk of squamous cell esophageal cancer and tumor location: an exploratory study. Clin Immunol, 128, 199-204. https://doi.org/10.1016/j.clim.2008.03.519
  23. Wang Y, Guo W, He Y, et al (2007). Association of MTHFR C677T and SHMT(1) C1420T with susceptibility to ESCC and GCA in a high incident region of Northern China. Cancer Causes Control, 18, 143-52. https://doi.org/10.1007/s10552-006-0097-4
  24. Wilcken B, Bamforth F, Li Z, et al (2003). Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world wide. J Med Genet, 40, 619-25. https://doi.org/10.1136/jmg.40.8.619
  25. Yang CX, Matsuo K, Ito H, et al (2005). Gene-environment interactions between alcohol drinking and the MTHFR C677T polymorphism impact on esophageal cancer risk: results of a case-control study in Japan. Carcinogenesis, 26, 1285-90. https://doi.org/10.1093/carcin/bgi076
  26. Zhang ZG, Rustum YM (1992). Pharmacologic rationale for fluoropyrimidine-leucovorin combination: biochemical mechanisms. Semin Oncol, 19, 46-50.
  27. Zhang M, Xie X, Lee HA, et al (2004). Soy and isoflavone intake are associated with reduced risk of ovarian cancer in southeast China. Nutr Cancer, 49, 125-30. https://doi.org/10.1207/s15327914nc4902_2

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